Single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 gene is associated with gallstone disease in Han Chinese.

BACKGROUND AND AIMS: Gallstone disease (GD) is a common disease of multigenetic origin; however, the major susceptibility loci for GD in human populations remain unidentified. This study aimed to identify the genetic factors contributing to gallstone development in Chinese. METHODS: A genome-wide scan was conducted in 12 Han Chinese GD families to identify linkage loci. The linkage region showing the highest logarithm of odds score encompasses the sterol 12α-hydroxylase gene (CYP8B1). Replication analysis with an independent sample of 192 GD patients and 192 unrelated, matched controls was carried out to verify the associations between CYP8B1 polymorphisms and GD. RESULTS: Three loci (D3S1266, D4S406, and D9S1682) showed suggestive or nominal evidence of linkage in all 12 GD families. The logarithm of odds score of D3S1266 reached 2.71 in the families with late-onset patients. The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 showed significant association to GD (P = 0.022), and carriers of the A allele had lower risk of GD (odds ratio = 1.46, 95% confidence interval: 1.055-2.034) compared with carriers of the G allele. CONCLUSIONS: The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of the CYP8B1 gene is associated with risk of GD in Chinese Han and appears to be responsible for the observed linkage with D3S1266.

Clinical features and outcomes of patients with severe acute pancreatitis complicated with gangrenous cholecystitis.

BACKGROUND: The effects of gangrenous cholecystitis (GC) and consequent surgical interventions on the clinical outcomes and prognosis of patients with severe acute pancreatitis are not clear. The present study was to characterize the clinical outcomes of patients with severe acute pancreatitis complicated with GC. METHODS: We retrospectively analyzed 253 consecutive patients hospitalized for acute pancreatitis in intensive care unit. Among them, 68 were diagnosed as having severe acute pancreatitis; 10 out of the 68 patients had GC. We compared these 10 patients with GC and 58 patients without GC. The indices analyzed included sepsis/septic shock, pancreatic encephalopathy, acute respiratory distress syndrome, acute renal failure, multiple organ dysfunction syndrome, and death. RESULTS: Specific CT images of GC in patients with severe acute pancreatitis included enlarged and high-tensioned gallbladder, wall thickening, lumenal emphysema, discontinuous and/or irregular enhancement of mucosa, and pericholecystic effusion. The rates of severe sepsis/septic shock (70.0% vs 24.1%, P<0.01), pancreatic encephalopathy (50.0% vs 17.2%, P<0.05), acute respiratory distress syndrome (90.0% vs 41.4%, P<0.01), multiple organ dysfunction syndrome (70.0% vs 24.1%, P<0.01), acute renal failure (40.0% vs 27.6%, P<0.05), and death (40.0% vs 13.8%, P<0.05) were significantly higher in patients with GC than in those without GC. CONCLUSION: CT scans can help to identify early GC in patients with severe acute pancreatitis; early diagnosis and intervention for patients with GC can reduce morbidity and mortality.

[Association of single nucleotide polymorphism in human CYP8B1 gene with gallstone disease].

OBJECTIVE: To identify the single nucleotide polymorphisms of human CYP8B1gene and explore the association of some of these SNPs with gallstone disease in Chinese population. METHODS: The exon and part of promoter were sequenced by a fluorescent labeling automatic method to identify and characterize the SNPs in Chinese population. For SNPs with an allelic frequency of over 10%, a case-control study was performed in patients and controls. RESULTS: Eleven SNPs were found within a 5119 bp region. Among them, 1 was in coding region, 5 in promoter and 5 in 3'-UTR. There were 3 novel SNPs and 12 SNPs in SNP database were not found. The allelic frequency of rs3732860 polymorphism showed a significant difference (P = 0.022) in the association study. The subjects with A allele had a significantly lower frequency of gallstone disease than those with G allele (OR = 1.465, 95%CI 1.055 - 2.034, P = 0.023). CONCLUSION: SNP rs3732860 of CYP8B1 gene is associated with gallstone disease in Chinese population. And A allele may play a protective role in the pathogenesis of gallstone.

HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver.

Niemann-Pick C1-like 1 (NPC1L1), a key regulator of intestinal cholesterol absorption, is highly expressed in human liver. Here, we aimed to gain more insight into mechanisms participating in its hepatic regulation in humans. Correlation analysis in livers from Chinese patients with and without gallstone disease revealed strong positive correlations between NPC1L1 and sterol regulatory element binding protein 2 (SREBP2) (r = 0.74, P < 0.05) and between NPC1L1 and hepatic nuclear factor alpha (HNF4alpha) (r = 0.53, P < 0.05) mRNA expression. HNF4alpha is an upstream regulator of HNF1alpha; thus, we also tested whether HNF1alpha participates in the regulation of NPC1L1. We showed a dose-dependent regulation by SREBP2 on the NPC1L1 promoter activity and mRNA expression in HuH7 cells. Chromatin immunoprecipitation assay confirmed the binding of SREBP2 to the promoter in vivo. Surprisingly, HNF4alpha slightly decreased the NPC1L1 promoter activity but had no effect on its gene expression. By contrast, HNF1alpha increased the promoter activity and the gene expression, and an important HNF1 binding site was identified within the human NPC1L1 promoter. ChIP assays confirmed that HNF1alpha can bind to the NPC1L1 promoter in vivo.

Decreased NPC1L1 expression in the liver from Chinese female gallstone patients.

BACKGROUND: Cholesterol gallstone disease is a very common disease in both industrialized and developing countries. Many studies have found that cholesterol gallstones are more common in women than men. The molecular mechanisms underlying the relationship between female gallstone disease and hepatic sterol transporters are still undergoing definition and have not been evaluated in humans. AIMS: The aim of this study is to probe for underlying hepatic molecular defects associated with development of gallstones in female. METHODS/RESULTS: Fifty-seven nonobese, normolipidemic Chinese female gallstone patients (GS) were investigated with 12 age- and body mass index-matched female gallstone-free controls (GSF). The bile from the female GS had higher cholesterol saturation than that from the female GSF. The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels. Consistently, immunohistochemistry showed decreased NPC1L1 expression in female GS. CONCLUSIONS: The decreased hepatic NPC1L1 levels in female GS might indicate a downregulated reabsorption of biliary cholesterol in the liver, which, in turn, leads to the cholesterol supersaturation of bile. Our data are consistent with the possibility that hepatic NPC1L1 may be mediated by SREBP2.

[Investigation of distribution of bacteria and fungi in severe acute pancreatitis].

OBJECTIVE: To investigate the spectrum of bacteria and fungi in different sites in severe acute pancreatitis (SAP). METHODS: The prospective study was performed in 205 patients with SAP treated from January 2000 to December 2008. The Infection rate of bacteria and fungi was observed prospectively in pancreatic necrosis and(or) pus form abdomen, body fluids and deep vein catheter in SAP. Body fluids and pancreatic necrosis were cultured twice a week. Central venous catheter was cultured when it had been placed for two weeks. Blood was cultured for bacteria and fungi when body temperature was more than 39 degrees C. Constituent ratio of bacteria and fungi was observed in different sites and in all sites within 28 days after onset of SAP. RESULTS: There were 937 pathogens, among which infection rates of gram-negative bacteria was higher than gram-positive bacteria and fungi (P < 0.05), the infection rates of gam-positive bacteria and fungi were similar. Infection rates of gram-negative bacteria in pancreatic necrosis (55.2%), bile (55.4%), blood (68.1%) and central venous catheter (44.4%) were increased significantly (P < 0.05) compared with gram-positive bacteria and (30.2%, 33.9%, 23.4%, 38.9%) and fungi (14.6%, 10.7%, 8.5%, 16.7%); however, infection rate of fungi (59.6%) was increased significantly (P < 0.05) compared with gram-negative bacteria (24.0%) and gram-positive bacteria (16.3%) in urine; infection rate of gram-negative bacteria (53.2%) was significantly higher (P < 0.05) than that of fungi (27.1%) and gram-positive bacteria (19.7%) in sputum. Infection rate of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) in gram-negative bacteria in pancreatic necrosis, bile, blood, central venous catheter and sputum was significantly higher than that of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae) (P < 0.01); infection rate of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli) was higher significantly (P < 0.01) than that of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii). Infection rate of staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus was significantly higher (P < 0.05) than that of Enterococcus faecalis and Enterococcus faecium in pancreatic necrosis and sputum;but infection rate of Enterococcus faecium in bile and urine was significantly higher than other gram-positive bacteria (P < 0.05). There was not difference among gram-positive bacteria;however, infection rate of Staphylococcus epidermidis in central venous catheter was increased significantly (P < 0.05). Infection rate of candida mycoderma in pancreatic necrosis, bile, urine and sputum was significantly higher than that of tricho bacteria (P < 0.05). The peak of infection rate of microbes in body fluid was within 2 to 3 weeks. CONCLUSIONS: Constituent ratio in gram-negative, gram-positive bacteria and fungi as well as their species in different sites is diverse. The peak of infection rate of microbes is 2 to 3 weeks after onset of the disease.

Increased NPC1L1 and ACAT2 expression in the jejunal mucosa from Chinese gallstone patients.

The incidence of cholesterol gallstones is a very common disease. The aim of this study is to probe for underlying intestinal molecular defects associated with development of gallstones. Twelve Chinese patients with cholesterol gallstone disease (GS) and 31 gallstone-free (GSF) patients were investigated. Quantitation of mRNA levels for individual genes in mucosal biopsies from jejunum was carried out with real-time PCR. The frequency of two SNPs in the ABCG8 gene (Y54C and T400K) was determined by allelic discrimination. The intestinal mRNA expression of NPC1L1 and ACAT2 were significantly higher in GS than GSF (P<0.05). No differences were observed concerning the levels for plasma lipids, plant sterols and 7alpha-hydroxy-4-cholesten-3-one between GS and GSF. No correlations were observed between patients carrying the different genotypes for Y54C or T400K and their mRNA levels for ABCG5 or ABCG8. The increased NPC1L1 and ACAT2 mRNA levels in gallstone patients might indicate an upregulated absorption and esterification of cholesterol in the small intestine.

[Expression and regulation of megalin in gallbladder mucosa associated with cholesterol gallstone disease].

OBJECTIVE: To explore the relationship between expression and regulation of Megalin in gallbladder mucosa and cholesterol gallstone disease. METHODS: Gallbladder mucosa, gallbladder wall, bile, gallstone were collected from 29 patients with cholesterol gallstone disease (GS) and 12 patients with gallstone free (GSF). Lipids of bile and stone were measured by kits. Expression of Megalin and Cubilin was analyzed by Real-time PCR. GBC-SD cell line were treated with T0901317, 9-cis retinoic acid, chenodeoxycholic acid (CDCA), the agonists of LXR, RXR, FXR, respectively. Gene expressions were detected. RESULTS: Biliary cholesterol % molar and CSI increased significantly in GS group [(7.98 +/- 0.44) mol% vs (4.87 +/- 0.39) mol%, P < 0.01]. Megalin expression in GS group was significantly higher than that in GSF group (P < 0.05) and cubilin expression was similar between two groups. In vitro experiments showed that CDCA markedly increased expression of megalin. CONCLUSION: This study shows that the increased expression Megalin may help to increase cholesterol uptake in gallbladder and play a compensative role in GS. FXR may participate in the transcription regulating of Megalin.

[Studies on the cell markers of endothelial function in sepsis].

OBJECTIVE: To study the phasic changes of the number of circulating endothelial cells (CEC) and endothelial microparticles (EMP) during the process of sepsis. METHODS: Thirty-one patients with sepsis were divided into mild group (<9), moderate group (9-15) and severe group (>15) according to the acute physiology and chronic health evaluation II (APACHE II) scores after onset, and each group was further divided into survivors and non-survivors.The level of CEC, EMP and pro-inflammatory cytokines were determined on 1, 2, 3, 7, 14 days after onset. RESULTS: (1)The level of EMP, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the severe group were significantly higher than the mild group and moderate group (P<0.05 or P<0.01). The number of CEC in the severe group was significantly lower than the mild group and moderate group (P<0.05 or P<0.01). (2)The levels of CEC, EMP in the non-survivor and the survivor group were significantly higher with sepsis increased significantly; and the levels of EMP, pro-inflammatory in the non-survivor group were significantly higher than those of the survivor group (P<0.05 or P<0.01), but the levels of CEC, IL-4 and IL-10 in non-survivors were significantly lower than the survivors (P<0.05 or P<0.01). CONCLUSION: The levels of CEC and EMP in patients with sepsis increased significantly. They can not only serve as an index to reflect the severity of sepsis, but also have a prognostic value in patients with sepsis.

[Strategy of treatment with high-volume hemofiltration on severe acute pancreatitis and fulminant acute pancreatitis.].

OBJECTIVE: To investigate strategy of treatment of hemofiltration on severe acute pancreatitis (SAP) and fulminant acute pancreatitis (FAP). METHODS: One hundred and thirty patients with SAP and eighty-one patients with FAP treated with hemofiltration (HF) were prospectively observed from March 1997 to December 2008. Indications for HF, variables (time interval for hemofiltration), mode, therapeutic dosage, blood rate, heparin dosage and components of hemofiltration, therapeutic efficacy (time of disapearance of abdominal pain, intra-abdominal pressure and survival rate) and complications (incidence of bleeding and blood infection). RESULTS: All patients underwent high volume hemofiltration (HVHF) or hemodialysis-filtration (HDF) within 72 hours after onset of the disease. Dose of SAP and FAP was (53 +/- 6) mlxkg(-1)xh(-1) and (59 +/- 10) mlxkg(-1)xh(-1) (P < 0.05), respectively. Rate of short veno-venous hemofiltration in SAP (76.9%) was higher than that of FAP (38.3%) (P < 0.05); however, rate of continuous veno-venous hemofiltration (23.1%) was lower than that of FAP (37.0%) (P < 0.05). Rate of HDF was much higher in FAP than that of SAP. Low molecular weight heparin and heparin were both available to anticoagualte;but dosage required in patients with FAP was much higher than that of SAP (P < 0.05). Time intervals for amelioration of abdominal pain in SAP and FAP were (9 +/- 6) h and (15 +/- 10) h, respectively. Itra-abdominal pressure was decreased significantly at the end of hemofiltration compared to prior to hemofiltration in SAP and FAP (P < 0.05). Level of serum triglyceride decreased abruptly after adsorption (P < 0.05). Rate of operation within 28 days in SAP (73.8%) was lower than FAP (87.7%). The in-hospital survival rates in SAP and FAP were 88.5% and 67.9%, respectively. Amount of platelet decreased in patients with blood flow rate less than 240 ml/min was higher than that of more than 240 ml/min (P < 0.05). And incidence of blood stream infection and bleeding increased significantly (P < 0.05). CONCLUSIONS: HVHF and HDF used in SAP and FAP patients underwent conservative treatment within 72 hours, respectively, can increase survival rate significantly.

[A study on increased permeability and morphological changes in actin cytoskeleton and tight junction of vascular endothelial cells induced by tumor necrosis factor-alpha].

OBJECTIVE: To study the effect of human tumor necrosis factor-alpha (TNF-alpha) on permeability of human vascular endothelial cell (EA.hy926) monolayer and its mechanism. METHODS: 5, 10, 20 microg/L TNF-alpha was respectively added to the cultured endothelial cell monolayer for 24 hours, or 10 microg/L TNF-alpha for 6, 12, 24 hours. Human vascular endothelial cell (EA.hy926) monolayer permeability was measured by detecting fluorescence intensity of fluorescein isothiocyanate (FITC) labeled dextran. Immunofluorescence and laser confocal microscopy were used to assess vascular endothelial actin cytoskeleton (F-actin) and tight junction protein (ZO-1) distribution. Western blotting was used to assess ZO-1 expression. RESULTS: Compared with control group, TNF-alpha significantly increased endothelial permeability and induced F-actin redistribution and stress fiber formation with ZO-1 derangement. Gaps increased obviously between endothelial cells. Furthermore, Western blotting showed that TNF-alpha reduced ZO-1 expression in a dose- and time-dependent manner. CONCLUSION: TNF-alpha increased endothelial cell permeability by damaging integrity of endothelial barrier function.

[Detection of early organ dysfunction for the selection of treatment strategy on severe acute pancreatitis.].

OBJECTIVE: To investigate the severity related influencing factor and treatment strategy of severe acute pancreatitis with early organ dysfunction. METHODS: From July 2007 to December 2008, 167 patients with severe acute pancreatitis were treated in the Surgical Department of Ruijin Hospital. The relationships between the happening of early organ dysfunction and outcome of the patients were observed, with operative or nonoperative treatment strategy. RESULTS: Among 167 patients, 68 patients have early organ dysfunction, in which 39 with single organ dysfunction and 29 with multiple organ dysfunction. The early organ dysfunction were involved in 47.1% in cardiovascular system, 35.3% in lung and 29.4% in kidney. Aging (P < 0.05) and higher APACHE II score (P < 0.05) predicted a poor prognosis, which were benefit from early operation. CONCLUSIONS: The mortality of the patients with SAP is related to age, and the degree of organ dysfunction as well. In the first phase of the disease, the selection of operation depends on the trends and the degree of early organ dysfunction before infected necrosis happens, with the aid of SOFA score as a scale.

ATP binding cassette G8 T400K polymorphism may affect the risk of gallstone disease among Chinese males.

BACKGROUND: Supersaturation of bile with cholesterol is a primary step in the formation of cholesterol gallstones. ATP binding cassette (ABC) G5 and G8 play an important role in regulating sterol absorption and secretion. To investigate a possible association between transporter gene polymorphism and gallstone formation, we examined five common polymorphisms in the ABCG5 (Q604E) and ABCG8 (D19H, Y54C, T400K, A632V) genes in patients with gallstone disease (GS). METHODS: Study subjects included 287 patients with GS and 219 gallstone free controls (GSF). Polymorphisms were determined using PCR-RFLP analysis or the Taqman MGB assay. Plasma and biliary lipid levels were measured. RESULTS: 2 SNPs of ABCG8 gene (Y54C and T400K) showed strong linkage disequilibrium (D'=0.824, r2=0.579). Male carriers of the less frequent K allele of ABCG8 T400K had a 2.31-fold elevated risk [95% confidence interval (CI) 1.12 approximately 4.76, P=0.023] for gallstone disease compared to male with the common genotype after the adjustment for age, body mass index. Males with the K allele had lower plasma triglyceride (P=0.044) and biliary phospholipid (P=0.035) levels than TT homozygotes. No such association was found in female or other 4 SNPs. CONCLUSIONS: These findings indicate that the T400K polymorphism in ABCG8 may be associated with the incidence of gallstone disease in males.

[Studies on the temporal profile of expression and release of major pro-inflammatory cytokines in vital organs following hemorrhagic shock].

OBJECTIVE: To study the kinetics of expression and release of major pro-inflammatory cytokines in the vital organs after hemorrhagic shock. METHODS: Eighty Sprague-Dawley (SD) rats were randomly divided into hemorrhagic shock group (n=40) and control group (n=40). Eight rats were sacrificed at 30, 60 and 90 minutes respectively after shock and 30 and 90 minutes respectively after resuscitation. The expressions of mRNA of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in intestine, liver, lung tissues were assessed by reverse transcription-polymerase chain reaction (RT-PCR), and the release of TNF-alpha and IL-6 in blood serum were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1)The pro-inflammatory cytokines were not increased in intestine, liver and lung tissues at 30 minutes after shock. The TNF-alpha mRNA expression was first up-regulated in the intestine at 60 minutes after shock (P<0.05), followed by the liver at 90 minutes after shock (P<0.01) and then the lung at 30 minutes after resuscitation (P<0.05). The TNF-alpha mRNA expressions in intestine, liver and lung tissues were higher at 90 minutes after resuscitation compared with those of control group (all P<0.01). The expressions of mRNA of TNF-alpha, IL-1 beta, IL-6 in the vital organs could be successively increased after hemorrhagic shock and resuscitation, with the TNF-alpha mRNA expression being the earliest, followed by the IL-1 beta mRNA and IL-6 mRNA. (2)The levels of TNF-alpha were increased in portal bloodstream prior to peripheral blood, and TNF-alpha preceded IL-6 at 60 minutes after shock (P<0.05), while there were no significant differences in the levels of TNF-alpha and IL-6 in portal bloodstream and peripheral blood at 30 minutes after shock, but they were higher than those of control group at 90 minutes after shock and at 30 and 90 minutes after resuscitation (all P<0.01). CONCLUSION: There is gut-liver-lung axis in the kinetics of expression and release of major pro-inflammatory cytokines after hemorrhagic shock.

[Strategy of controlling fluid resuscitation for severe acute pancreatitis in acute phase].

OBJECTIVE: To investigate the strategy of controlling fluid resuscitation for severe acute pancreatitis (SAP) in acute phase. METHODS: From March 2001 to January 2006, 83 patients meeting for experimental criteria were included in this clinical trial. They were divided into early fluid expansion group (Group I, within 24 h after admission, 21 patients), middle fluid expansion group (Group II, within 25 - 48 h, 35 patients) and late fluid expansion group (Group III, within 49 - 72 h, 27 patients). Parameters of treatment of fluid therapy within 4 d after admission were observed. Serum lactic level was measured on admission and on meeting for criteria of fluid expansion. APACHEII scores, operation rate within 2 weeks, rate of mechanical ventilation, rate of ACS and survival rate were observed. RESULTS: Time interval for meeting fluid expansion criteria in Group I, Group II, Group III was (13 +/- 6) h, (38 +/- 5) h and (61 +/- 8) h, respectively. And there was statistical significance among them (P < 0.05). HCT (%) in Group I (33 +/- 6)% was lower than that of Group II (40 +/- 6)% and Group III (42 +/- 11)% significantly (P < 0.01) at the first day after admission; and there was no statistical significance between Group II and Group III. The amount of crystal and colloid infused in Group I (4014 +/- 2887) ml and (1220 +/- 705) ml at the day of admission was more than those of Group II (2366 +/- 1959) ml and (821 +/- 600) ml and Group III (2615 +/- 1574) ml and (701 +/- 585) ml (P < 0.01); but there was not different between Group II and Group III (P > 0.05). The ratio of colloid and crystal in Group III at the day of admission was lower than those of Group I and Group II (P < 0.05). The total amount of fluid infused was not different among 3 groups for the 4 d (P > 0.05). And infusion rate at the day of admission in Group I was more rapid than those of Group II and Group III (P < 0.05); and there was no difference between Group II and Group III (P > 0.05). The total amount of fluid sequestration in Group II for the 4 d was lower than those of Group I and Group III (P < 0.05); and there was no statistical significance between Group I and Group III (P > 0.05). At the first to the third day after admission APACHEII scores in Group I were higher than those of Group II and Group III (P < 0.05); and at the second and third day, APACHEII scores in Group III were higher than those of Group II (P < 0.05). Rate of mechanical ventilation in Group I (85.7%) was higher than those of Group II (37.1%) and group III (63.0%) (P < 0.05); and rate of ACS was most lowest in Group II (37.1%) (P < 0.05). Survival rate in Group I (38.1%) was lower than those of Group II (85.7%) and Group III (66.7%) (P < 0.05); and Group III was lower than that of Group II (P = 0.075). CONCLUSIONS: Within 72 h after onset of the disease, survival rate is improved significantly through controlling fluid resuscitation and prevention of body fluid sequestration.

[Long-term outcome and health-related quality of life in survivors of severe acute pancreatitis].

OBJECTIVE: To evaluate the health-related quality of life and postdischarge long-term outcome after severe acute pancreatitis. METHODS: The hospital records of patients with SAP discharged healthy from January 2003 to December 2003 were reviewed. The Rand 36-item Health Survey with accessory question was mailed to each patient. The means and deviations for each of eight scales scores of SF-36 were calculated, the study population scores were compared with general Chinese population; Univariate analysis was applied to determining the effects of variables such as age, sex, causes of disease, mode of treatment, frequency of surgery, financial burden, length of stay, chronic complications. Accessory questions were analyzed separately. RESULTS: The means and deviations for each of eight scales (PF, RP, RE, BP, VT, MH, SF, GH) scores of SF-36 in SAP patients were 83 +/- 15, 62 +/- 42, 69 +/- 36, 80 +/- 15, 69 +/- 19, 72 +/- 15, 75 +/- 18, 65 +/- 18, compared with general people. Except RP and SF, the others were similar. In the ANOVA of Physical Component Summary, the three variables mode of treatment, financial burden and length of stay were included (P < 0.05), while in that of Mental Component Summary, the two variables of gender and financial burden were included (P < 0.05). CONCLUSIONS: The health-related quality of life in SAP patients is similar to that of general people. Greater attention should be given to mode of treatment, length of stay and financial burden to improve quality of life.

[The characteristic of severe acute pancreatitis and the selection of the therapeutic strategy].

OBJECTIVE: To investigate the relationship between the clinical character and therapeutic strategy and prognosis in severe acute pancreatitis. METHODS: From January 2001 to December 2005, 783 patients with SAP were treated. Therapeutic strategy was selected based on the preliminary scheme for diagnosis and treatment of severe acute pancreatitis by pancreatic surgery society of CMA. All the patients were divided into biliary group and non-biliary group, while 375 patients in biliary group, with 182 patients treated operatively and 193 patients treated nonoperatively; and 408 patients in non-biliary group, with 147 patients treated operatively and 261 patients treated nonoperatively. RESULTS: There were 698 survivals, the overall survival rate was 89.1%. 357 survivals in the biliary SAP group, the survival rate was 95.0%, in which 171 survivals from operation treated cases, with the survival rate of 94.0%, and 186 survivals from non-operation treated cases, with the survival rate of 96.4%; 341 survivals in the non-biliary SAP group, the survival rate was 84.0%, in which 110 survivals from operation treated cases, with the survival rate of 74.8%, and 231 survivals from non-operation treated cases, with the survival rate of 88.5%. 48.3% patients of the survival group had organ dysfunction, and 18.3% patients had multiple organ dysfunctions, while 100% patients of the death group had organ dysfunction, and 97.6% patients had multiple organ dysfunction. Respiratory dysfunction was found to be the most common cause totally followed by nerve system dysfunction and shock, with the rates of 26.3%, 11.7% and 10.3%, respectively. Respiratory dysfunction, renal dysfunction and cardiac dysfunction are most commonly in death group, with the rate of 94.1%, 60.0% and 60.0%, respectively. The rate of fungi infection in the survival group and death group were 8.9% and 37.6%. The rates of alimentary tract fistula in the survival and death group were 0.9% and 14.1%, respectively. CONCLUSIONS: The therapy aiming at the cause for biliary SAP and the operation aiming at infected pancreatic necrosis is helpful to improve curative rate; MODS is the main cause of death in severe acute pancreatitis. Respiratory dysfunction, renal dysfunction and cardiac dysfunction are high risk factors.

[Therapeutic experience of fulminant acute pancreatitis in acute response stage].

OBJECTIVE: To investigate therapeutic strategy of fulminant acute pancreatitis (FAP) in acute response stage. METHODS: Sixty-four patients were divided into Death group (27 patients) and Survival group (37 patients). The time course of shock and recovery of enteral function, parameters of fluid resuscitation, PaO(2)/FiO(2) and AaDO(2) at 24 hours prior to mechanical ventilation, rate of continuous venovenous hemofiltration (CVVH) and abdominal compartment syndrome (ACS), severity of the disease in the acute response stage were investigated. And the effect of surgical manner and time on the prognosis was also analyzed. RESULTS: Compared with Survival group, the time course of shock and recovery of enteral function in Death group were prolonged significantly (P < 0.05). Between the groups, there was no difference in the amount of crystal fluid infused from admission to 72 hours after, but the amount of colloid fluid infused and ratio of amount of colloid and crystal fluid in Survival group were higher (P < 0.05). The amount of fluid retention in third space from admission to 72 hours after in Death group was higher than that of Survival group significantly (P < 0.05). The fluid infusing rate in Survival group in the first day of admission was faster than Death group (P < 0.05). PaO(2)/FiO(2) and AaDO(2) in 24 hours prior to mechanical ventilation in Death group were negatively changed significantly. Within 72 hours after the onset of the disease, the rate of CVVH in Survival group was higher than Death group. Incidence rate of ACS and the APACHEII scores within 72 hours after admission in Death group were higher than in Survival group. The cure rate of the patients operated in the day 7 to day 14 after admission was higher than that of patients operated prior and post this period. Time for the first operation in operated patients was earlier than patients received minimally invasive drainage (MID) and its cure rate was lower than that of MID Group. CONCLUSIONS: It is the key point to shorten the time course of ischemia, to control persistent systemic inflammatory response syndrome (SIRS) and to adopt reasonable surgical intervention in acute response stage for FAP.

[Study on the position of genes responsible for gallstone disease in Chinese population].

OBJECTIVE: To search the susceptibility genes of gallstone disease in Chinese population. METHODS: A genome wide scan was performed in twelve families with gallstone disease using fluorescence-labeled microsatellite markers. Genehunter and Batchlink of Linkage package were used for non- parameter and parameter linkage analysis to search the linkage loci on chromosomes. RESULTS: Four loci of D3S1266, D4S406, D9S1682 and D11S902 showed suggestive evidence for linkage. nonparametric linkage analysis (NPL)-score of D4S406 and D9S1682 was 1.77 (P = 0.05) and 1.92 (P = 0.04) respectively. The corresponding logarithm of the odds ratio (LOD)-score of D3S1266, D9S1682 were 1.35 and 2.07, and showed a rise of LOD-score from 1.35 to 2.71, 2.07 to 2.40 respectively when families with later-found patients or with higher triglyceride level were analyzed alone. Transmitted disequilibrium test of D11S902 showed a P-value of 0.0027. CONCLUSIONS: Chromosome 3, 4, 9 and 11 may contain genes involved in gallstone disease in Chinese population, and chromosome 3, 9 may hide genes that are liked to gallstone disease in families with later-found patients or with higher triglyceride concentration.

The NPC1L1 Polymorphism 1679C>G Is Associated with Gallstone Disease in Chinese Patients.

Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk.